1. Field of the Invention
Present methods of altering the electrolyte composition of research or clinical quantities of solutions of biological or medical origin have several disadvantages. Conventional dialysis in bags suffers from being very time consuming (typically 12 to 24 hours), involves complex knot tying and labeling and the risk of total loss of sample. Such conventional dialysis in bags also has a relatively high molecular weight cutoff size (typically 4,000 Daltons) making the dialysis of small macromolecules difficult. During dialysis the osmotic pressure drives water through the dialysis membranes and into the bags, resulting in dilution of the product. Large quantities of rinsing (receiving) solution are required and hence dialysis exchanges wastes from a smaller to a much larger volume.
Diafiltration also generally suffers from a high molecular weight cutoff (typically 10,000 Daltons) and a long processing time (typically up to an hour) and often requires use of a centrifuge.
It is therefore an objective of this invention to provide apparatus which suffers from none of the disadvantages of prior art apparatus and in which processing time can be of the order of minutes rather than hours or days.
Another objective is to provide apparatus in which the handling of milliliter or microliter quantities of sample can be accomplished with laboratory pipettes or syringes.
A further objective is to provide apparatus for altering the electrolyte composition of research or clinical quantities of solutions of biological or medical origin in which the molecular weight cutoff can be 300 Daltons or even less.
Yet a further objective is to provide apparatus for altering the electrolyte composition of milliliter quantities of solutions of low molecular weight compounds such as amino acids, polypeptides and oligonucleotides, all of which would be substantially lost during processing in prior art apparatus.
These and other objectives are accomplished in a non-flowing batch electrodialysis apparatus comprising:
a vessel, tank or box containing anode and cathode means spaced apart horizontally; PA1 at least one demountable, rigid pocket cell having an opening for filling the cell at the top of the cell, said pocket cell positioned between said anode and cathode means and itself comprising at least two parallel spaced apart electrolytically conducting hydraulic barriers or membranes oriented substantially vertically and substantially parallel to said anode and cathode means, at least one of said barriers in each continguous pair in each pocket cell being ion-selective; PA1 means for preventing leakage of liquids along at least the lateral and lower edges of each said pocket cell to and/or from the interior of said vessel and the interior, liquid holding cavity of said pocket cell, each said cavity being narrower at the bottom than at the top; means for inhibiting the bypass of electric current between said anode and cathode means around the lateral and lower edges of said pocket cell when said vessel is filled with an electrolytically conducting solution to a level below the opening at the top of each said pocket cell and an electric current is applied between said anode means and said cathode means.
2. Description of the Prior Art
Electrodialysis (frequently referred to herein as "ED") has become an accepted apparatus for transferring electrolytes from one solution to another. The state of the art is well described in pages 726 through 738, Volume 8, Kirk-Othmer Encyclopedia of Chemical Technology, 3d Edition, Wiley, N.Y. 1979. Typically 100 or more pairs of spaced electrolytically conducting hydraulic barriers (membranes) are arrayed in parallel between a pair of electrodes. In each pair of contiguous barriers, one barrier has a transport number for ions of one sign substantially greater than that of the above mentioned solutions and of that of the other barrier in said pair. Said substantially selective barriers alternate in the array with barriers which are less selective for the above mentioned ions of one sign. Solutions of electrolyte(s) are introduced into narrow spaces between the barriers and between the electrodes and the barriers adjacent thereto. A direct electric current (which may have some alternating current component) is applied between the electrodes causing electrolyte to be transferred from every other space to the intervening spaces. Electrolyte enriched solution is withdrawn from the latter spaces and electrolyte depleted solution from the former.
None of the above prior art apparatus is satisfactory for the rapid removal of electrolytes from small volumes of solution containing valuable proteins, polypeptides, oligonucleotides and the like.
It is therefore an objective of this invention to provide ED apparatus for rapidly and conveniently demineralizing small volumes of solutions of biological or medical origin which apparatus avoids the loss of valuable or noxious permeates (e.g. carcinogens) into large volumes of receiving (permeate) solution.
This and other objectives will become clear from the following brief description of the drawings and description of preferred embodiments.